Métabolisme

<p>2-Phenyl-2-(2-pyridyl)acetonitrile represents the principal metabolite of the antigastric agent SC 15396, produced by the supernatant fraction of rat liver</p>

<p>Temocaprilat (RS5139) is an Angiotensin-converting Enzyme (ACE) inhibitor.</p>

<p>244cis, an ionizable cationic lipid incorporating a piperazine structure, facilitates the creation of lipid nanoparticles (LNPs). These LNPs, when formulated with 244cis and coated with an mRNA reporter gene, exhibit preferential accumulation in the lungs of mice, in contrast to those formulated with SM-102. Additionally, it leads to a reduction in the levels of serum chemokine (C-C motif) ligand 2 (CCL2) [1].</p>

<p>Lignoceroyl ethanolamide, a fatty N-acyl ethanolamine within the endocannabinoid family, is derived from lignoceric acid, which is found in relatively high concentrations in rat cerebrospinal fluid. However, the specific function and significance of this metabolite remain unclear.</p>

<p>113-O16B, an ionizable cationic lipidoid featuring a disulfide bond, is utilized in producing lipid nanoparticles (LNPs) for mRNA delivery [1].</p>

<p>GSK2256294A (GSK 2256294) is potent, selective inhibitor of recombinant human, rat and mouse sEH with IC50 of 27 pM, 61 pM and 189 pM, respectively.</p>

<p>Palmitoleic acid, an ω-7 monounsaturated fatty acid found in macadamia and sea buckthorn oils, enhances both basal and insulin-stimulated glucose uptake, as well as Glut4 protein levels in 3T3-L1 adipocytes at a 200 µM concentration. Ex vivo, at a dosage of 300 mg/kg per day, it significantly increases glucose uptake and both aerobic and anaerobic glycolysis, while decreasing de novo fatty acid synthesis and the activity of lipogenic enzymes, specifically ATP citrate lyase (ACL) and glucose-6-phosphate dehydrogenase (G6PDH), in isolated murine adipocytes. Furthermore, the dietary administration of palmitoleic acid at 300 mg/kg mitigates high-fat diet-induced insulin resistance and liver inflammation in mice.</p>

<p>Monoacylglycerol lipase inhibitor 1, also known as compound 13 [1], is a potent inhibitor of monoacylglycerol lipase.</p>

<p>PDE7-IN-3 (Example 2) serves as an inhibitor of phosphodiesterase PDE7 and exhibits potential analgesic properties.</p>

Inz-1 is an effective and fungal-selective inhibitor of mitochondrial cytochrome bc1 with IC50s of 8.092 and 45.320 μM for yeast and human.

Gisadenafil besylate (UK 369003-26) is a potent and orally active PDE5 inhibitor, for lower urinary tract symptoms associated with benign prostatic hyperplasia.

<p>ICMT-IN-42 (compound 21) serves as an ICMT inhibitor, demonstrating potency with an IC50 of 0.054 μM [1].</p>

<p>Oseltamivir acid methyl ester, a CES1-convertible neuraminidase inhibitor, serves as an antiviral prodrug.</p>

<p>1,2-Dioleoyl-3-stearoyl-rac-glycerol, a triacylglycerol, features oleic acid at the sn-1 and sn-2 positions and stearic acid at the sn-3 position. This compound is present in sunflower, corn, and soybean oils, as well as in ostrich oil.</p>

<p>9(Z),11(E)-Conjugated Linoleic Acid Methyl Ester, identified in lemon grass (C. flexuosus), serves as a standard for quantifying conjugated linoleic acids in thermally stressed olive oil and trans fats in bakery products. [Matreya, LLC. Catalog No. 1255]</p>

<p>C12-113, a lipidoid delivery agent, effectively transfects siRNA into cells and, when combined with additional lipids, forms lipid nanoparticles (LNPs). These LNPs facilitate the delivery of mRNA encoding the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice [1] [2].</p>

<p>JW 618 is a selective inhibitor of ABHD6, demonstrating inhibition concentrations (IC50 values) of 38 nM for mouse ABHD6 and 13 nM for rat ABHD6, indicating its potent activity across species [1].</p>

<p>GLX481304 is a selective Nox-2 and Nox-4 inhibitor, exhibiting IC50 values of 1.25 μM.</p>

<p>20-HETE Inhibitor-1 (Comp 83) serves as an inhibitor of 20-HETE formation [1].</p>

<p>JNJ-40929837 is an oral inhibitor of LTA4 hydrolase, which catalyzes LTB4 production.</p>

<p>(S)-(-)-Bay-K-8644 ((S)-(-)-Bay K 8644) is an agonist of L-type Ca2+ channel and activates Ba2+ currents with an EC50 of 32 nM.</p>

<p>Tetrahydro-11-dehydrocorticosterone is an inhibitor of 11β-hydroxysteroid dehydrogenase [1].</p>

<p>ICMT-IN-1 (compound 75) is a potent ICMT inhibitor with an IC50 value of 0.0013 μM.</p>

<p>Thioquinapiperifil is a type of phosphodiesterase-5 (PDE-5) inhibitor found in dietary supplements.</p>

TMP778 is an effective and selective RORγt inverse agonist (IC50: 7 nM in FRET assay).

<p>Nampt-IN-10 TFA, a NAMPT inhibitor, shows potency in A2780 (IC50: 5 nM) and CORL23 (IC50: 19 nM), suitable for ADC payloads.</p>

<p>NC1 is a potent allosteric inhibitor of lymphoid-specific PTPN22, a protein tyrosine phosphatase.</p>

<p>ICMT-IN-9 (compound 47) is a potent ICMT inhibitor with an IC50 value of 0.16 μM [1].</p>

<p>Glucocerebrosidase-IN-1 (compound 11a) hydrochloride is a potent, selective GCase (glucocerebrosidase) inhibitor with IC50 and Ki values of 29.3 μM and 18.5 μM</p>

<p>CETP-IN-3 is an inhibitor of the plasma glycoprotein cholesterol ester transfer protein (CETP), elevating HDL-C through inhibition of CETP.</p>

FTI-2153 inhibits farnesyltransferase with 1.4 nM IC50, >3000x more effective on H-Ras than Rap1A.

<p>GSK2647544 inhibits Lp-PLA2, a pro-inflammatory enzyme from macrophages, orally active, calcium-independent.</p>

<p>Prostaglandin B2 is a dehydration product of PGE2/PGA2 with weak TP receptor activity, raising rabbit pulmonary pressure at &gt;5 ug/kg.</p>

<p>PPARδ agonist 9 (compound 21), with an EC50 of 3.6 nM, is effective in vivo, decreasing serum MCP-1 concentrations in mice and markedly reducing atherosclerotic</p>

<p>EMD638683 is a highly selective SGK1 inhibitor with IC50 of 3 μM. EMD638683 R-Form is the R-form of EMD638683.</p>

<p>AZD7687: Selective DGAT1 inhibitor, IC50 of 80 nM. In vitro reduces postprandial TAG. In vivo significant GI side effects at &gt;5 mg/day dose.</p>

<p>Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a class of endogenous lipids whose levels are modulated by fasting and high-fat diets and are linked to insulin sensitivity. These compounds typically consist of a C-16 or C-18 fatty acid, such as palmitoleic, palmitic, oleic, or stearic acid, esterified to a hydroxylated C-16 or C-18 lipid. One specific form of FAHFA, known as 9-OAHSA, involves the esterification of oleic acid to 9-hydroxy stearic acid. Within the FAHFA family, OAHSAs notably represent the predominant form found in the serum of glucose-tolerant AG4OX mice, which uniquely overexpress the Glut4 glucose transporter in adipose tissue.</p>

<p>CAY10502 inhibits cPLA2α (85 kDa), crucial in inflammation/arachidonic cascade, with 4.3 nM IC50, reducing arachidonic acid in human platelets.</p>

<p>N-Desethyl Brinzolamide oxalate functions as a dual inhibitor targeting Carbonic anhydrase II and Carbonic anhydrase IV, exhibiting inhibitory concentrations (IC50) of 1.28 nM and 128 nM, respectively [1].</p>

<p>Me-Indoxam is an inhibitor of sPLA2. It has no effect on arachidonic acid release and platelet activating factor synthesis.</p>

<p>Ilepatril, also known as AVE-7688, is a vasopeptidase inhibitor for the treatment of hypertension.</p>

<p>ICMT-IN-25 (compound 37) serves as a potent inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), exhibiting an IC50 value of 0.025 μM [1].</p>

<p>HSD17B13-IN-2 (compound 1) serves as a potent inhibitor of hydroxysteroid 17ß-dehydrogenase 13 (HSD17B13) with demonstrable activity in cellular experiments [1</p>

<p>C16 1-Deoxyceramide (m18:1/16:0) is a lipid molecule that can be used in life science related research. The CAS number of C16 1-Deoxyceramide (m18:1/16:0) is 1246298-56-5.</p>

<p>1,2-Dipropionyl-sn-glycero-3-phosphocholine (PC) is a phospholipid characterized by the presence of propionic acid at its sn-1 and sn-2 positions. This compound has applications in the investigation of interactions between water and the phosphocholine headgroup in aqueous solutions.</p>

<p>ICMT-IN-38 (Compound 42) is an ICMT inhibitor, demonstrating an IC50 value of 0.049 μM [1].</p>

<p>GLUT4 activator 1 is a potent glucose transporter type 4 (GLUT4) translocation activator (EC50: 0.14 μM).</p>

<p>Imiglitazar (TAK559) is a potent PPAR-β/δ receptor agonist with hypoglycemic effects.</p>

<p>Difamilast is a selective inhibitor of phosphodiesterase-4 (PDE4) with particularly efficient inhibition of subtype B (IC50=11.2 nM).</p>

<p>OSMI-2 is a cell-permeable inhibitor of O-linked N-acetylglucosamine transferase (OGT).</p>

<p>2-Myristyl dipalmitin (PMP), a triglyceride of palmitic acid, shows potential as a lipid marker for Wilson's disease (WD) [1] [2].</p>

<p>ICMT-IN-26 (compound 38) acts as an ICMT inhibitor with an IC50 value of 0.36 μM [1].</p>

<p>11-Dehydro Thromboxane B3 (11-dehydro TXB3) serves as a urinary metabolite of TXA3 in humans following an increased dietary intake of EPA.</p>

<p>GNE-618 is a potent and orally active inhibitor of nicotinamide phosphoribosyltransferase (IC50: 6 nM).</p>

<p>Fatty acid amide hydrolase (FAAH), an enzyme responsible for the hydrolysis and inactivation of fatty acid amides like anandamide and oleamide, has been identified as a target by the potent FAAH inhibitor PHOP. PHOP demonstrates remarkable inhibitory activity with K_i values as low as 0.094 nM for human FAAH and 0.2 nM for rat FAAH. Additionally, through a proteomics assay focusing on the serine hydrolase enzyme family, to which FAAH belongs, PHOP's selectivity was evaluated, presenting IC_50 values of 1.1 nM against FAAH, 1.4 nM against triacylglycerol hydrolase (TGH), and greater than 100 µM against an uncharacterized hydrolase (KIAA1363). This specificity profile of PHOP underscores its potential for yielding precise outcomes in studies involving complex biological systems.</p>

KCL-286 is an available and potent retinoic acid receptor beta agonist for the amelioration of spinal cord injury (SCI).

Fasidotril inhibits NEP/ACE, treats high blood pressure in rats, effective in humans with hypertension.

<p>MetAP2-IN-1 is a selective inhibitor of MetAP2, a target involved in angiogenesis-related conditions, suitable for research applications [1].</p>

<p>BI-11634 is a factor Xa inhibitor.</p>

IDH1 Inhibitor 3 is a mutant isocitric dehydrogenase 1 (IDH1) inhibitor (IC50: 45 nM for IDH1R132H).

<p>CMI-392 is a dual 5-lipoxygenase inhibitor and platelet-activating factor (PAF) receptor antagonist (IC50s: 100 and 10 nM).</p>

<p>3-Hydroxycarbofuran, a principal metabolite of Carbofuran, acts as a reversible inhibitor of acetylcholinesterase (AChE) [1].</p>

<p>Efipladib is a phospholipase inhibitor. Efipladib decreases nociceptive responses without affecting PGE2 levels in the cerebral spinal fluid.</p>

<p>C18 ((±)-2'-hydroxy) Ceramide (d18:1/18:0) is a lipid molecule that can be used in life science related research. The CAS number of C18 ((±)-2'-hydroxy) Ceramide (d18:1/18:0) is 34249-41-7.</p>

<p>1-Oleoyl-2-hydroxy-sn-glycero-3-PG (sodium salt), a lysophospholipid with oleic acid (18:1) at the sn-1 position, finds application in creating micelles, liposomes, and various artificial membranes, notably in lipid-based drug delivery systems.</p>

GSK2973980A is a selective Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitor (IC50: 3 nM).

<p>DGAT1-IN-1 is a potent inhibitor of diacylglycerol O- acyltransferase type 1(DGAT1, IC50 of &lt; 10 nM).</p>

<p>PDE12-IN-3 is an inhibitor of phosphodiesterase 12 (PDE12) (pXC50 of 7.68),with antiviral activity.</p>

<p>ICMT-IN-14 (compound 50) serves as an inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), exhibiting potent activity with an IC50 of 0.025 μM [1].</p>

<p>ICMT-IN-52 (compound 44) serves as an ICMT inhibitor with an IC50 value of 0.052 μM [1].</p>

<p>14,15-Epoxyeicosatrienoic acid (14,15-EET), derived from Arachidonic acid metabolism, significantly inhibits platelet aggregation in vivo and enhances</p>

<p>1,2-Dipalmitoyl-sn-glycero-3-N,N-dimethyl-PE is a derivative of 1,2-dipalmitoyl-sn-glycero-3-PE (1,2-DPPE) with two added methyl groups on its sn-3 moiety, which in aqueous suspensions, reduces the phase transition temperature relative to those of 1,2-DPPE and 1,2-dipalmitoyl-sn-glycero-3-N-methyl-PE (1,2-NMeDPPE). It is utilized in creating liposomes and monolayers for investigating membrane permeability and monolayer viscosity.</p>

<p>COX-2-IN-30, a benzenesulfonamide derivative, is an orally active, dual inhibitor of cyclooxygenase-2 (COX-2; IC50 = 49 nM) and cyclooxygenase-1 (COX-1; IC50 =</p>

<p>1-Stearoyl-2-hydroxy-sn-glycero-3-PG, a lysophospholipid characterized by the presence of stearic acid (18:0) at the sn-1 position, finds application in the creation of micelles, liposomes, and various artificial membranes, including those utilized in lipid-based drug delivery systems.</p>

<p>15-PGDH-IN-2 (Compound 2) is an inhibitor of 15-PGDH with an IC50 value of 0.274 nM. This compound is useful for research into hair loss, bone formation, gastric ulcer healing, and dermal wound healing [1].</p>

<p>3-Oxo-5β-cholanoic acid (Dehydrolithocholic acid) (Dehydrolithocholic acid) is a bile acid metabolite and inhibits the differentiation of TH17 cells by directly</p>

<p>Lp-PLA2-IN-9, a tetracyclic pyrimidinone, inhibits rhLp-PLA2 (pIC50: 10.1), promising for neurodegenerative research.</p>

<p>1-Myristoyl-2-linoleoyl-3-oleoyl-rac-glycerol, a triacylglycerol, features myristic acid, linoleic acid, and oleic acid at the sn-1, sn-2, and sn-3 positions, respectively. This compound is prevalent in mature human milk, infant formula fats, and butterfat.</p>

<p>5(S)-HETrE, made by 5-LO from mead acid, has unknown biological activity and metabolic fate.</p>

<p>UK 357903, a phosphodiesterase 5A (PDE5A) inhibitor, is used potentially for the treatment of erectile dysfunction.</p>

<p>PDE5-IN-2 is a potent, highly selective, and orally active inhibitor of PDE5(IC50 of 0.31 nM)</p>

<p>MSI-1436 is a selective, non-competitive the enzyme protein-tyrosine phosphatase 1B (PTB1B)inhibitor(IC50 of appr 1 μM)</p>

<p>SHP2-IN-19 (compound 183) is a SHP2 inhibitor exhibiting potent activity with an IC50 of 3 nM, and is utilized in glioblastoma research [1].</p>

<p>Ac-VDVAD-CHO is an inhibitor of caspase-2 and caspase-3 (IC50: 46 nM for caspase-2 and 15 nM for caspase-3) [1].</p>

<p>AZD1092 is the glucokinase enzyme activator.</p>

<p>Prolyl Hydroxylase inhibitor 1 is an orally active inhibitor of hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) (IC50 of 62.23 nM).</p>

<p>ICMT-IN-33 (compound 73) functions as an ICMT inhibitor with an IC50 value of 0.46 μM [1].</p>

<p>(±)-HIP-A is an excitatory amino acid transporter blocker.</p>

<p>1,2-Dilinoleoyl-sn-glycero-3-PC (Dilinoleoyllecithin), a phospholipid, finds application in the production of artificial membranes [1].</p>

<p>L-hydroxylysine dihydrochloride , is formed by posttranslational hydroxylation of some lysine residues. It is an amino acid, is exclusive to collagen protein.</p>

<p>Gisadenafil (UK-369003) is a selective inhibitor of phosphodiesterase 5 (PDE5) with an IC50 of 3.6 nM and prevents degradation of cGMP.</p>

<p>RORγt Inverse agonist 6 is an agonist of RORγt inverse. RORγt Inverse agonist 6 can be used in research on Th17-driven autoimmune diseases.</p>

<p>NOX2-IN-2 (compound 33) is a potent inhibitor of NOX2, disrupting the p47phox-p22phox protein-protein interaction with a dissociation constant (K i) of 0.24 μM.</p>

<p>1,2-Dilauroyl-sn-glycero-3-phospho-(2R)-glycerol is a type of phosphoglycerol characterized by the presence of lauric acid at the sn-1 and sn-2 positions. [Matreya, LLC. Catalog No. 1443]</p>

<p>ICMT-IN-54 (compound 7c), an adamantyl analogue, serves as an ICMT inhibitor with an IC50 value of 12.4 μM, targeting the methylation process facilitated by</p>

<p>ATX-001, an ionizable cationic lipid, is utilized in the creation of lipid nanoparticles (LNPs) for mRNA delivery [1].</p>

<p>Safinamide acid, a potential impurity in commercial safinamide preparations and a degradation product of safinamide under thermal and oxidative stress, is encountered in the pharmaceutical formulation process.</p>

<p>"113-O12B is an ionizable cationic lipidoid containing a disulfide bond, utilized in the generation of lipid nanoparticles (LNPs) for mRNA delivery [1]."</p>

<p>Magmas-IN-1 (compound 9), a small molecule Magmas inhibitor (SMMI), targets the mitochondria-associated granulocyte-macrophage colony-stimulating factor (GM-CSF</p>

<p>ICMT-IN-37 (compound 41) serves as an inhibitor of ICMT with an IC50 value of 0.308 μM [1].</p>